Nortriptyline interactions
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Nortriptyline Interactions: A Comprehensive Overview
Nortriptyline and Thioridazine Interaction
Elevated Plasma and Brain Concentrations
When nortriptyline is administered in combination with thioridazine, plasma drug concentrations are significantly higher compared to when nortriptyline is given alone, regardless of the administration route (oral, intraperitoneal, or intravenous) . This combination also results in elevated nortriptyline concentrations in the brain and prolongs its half-life in brain tissue .
Enhanced Hypothermic Effects
The combination of nortriptyline and thioridazine produces greater hypothermic effects than either drug alone, which is likely due to their combined pharmacologic actions. This interaction may also relate to the increased lethality observed with this drug combination .
Nortriptyline and Rifampin Interaction
Induction of Metabolism
Rifampin, a known inducer of the hepatic cytochrome P450 system, significantly affects the metabolism of nortriptyline. Concurrent administration of rifampin results in undetectable serum concentrations of nortriptyline, which dramatically increase after rifampin is discontinued . This interaction underscores the need for careful monitoring and potential dosage adjustments when these drugs are co-administered.
Nortriptyline and Terbinafine Interaction
Inhibition of CYP2D6
Terbinafine inhibits the CYP2D6 enzyme, which is crucial for the metabolism of nortriptyline. This inhibition leads to increased plasma concentrations of nortriptyline, potentially reaching toxic levels. The interaction is prolonged, with significant increases in the area under the curve (AUC) of nortriptyline even months after terbinafine cessation 59. This interaction necessitates careful clinical management and monitoring of nortriptyline levels during and after terbinafine treatment.
Nortriptyline and Valpromide Interaction
Increased Bioavailability
Valpromide, often used in the treatment of affective disorders, significantly increases the plasma concentrations of nortriptyline when co-administered. This interaction results in higher bioavailability of nortriptyline, necessitating dosage adjustments to avoid potential toxicity .
Nortriptyline and Cytochrome P450 Enzymes
Risk of Accidental Poisoning
The metabolism of nortriptyline is heavily influenced by various cytochrome P450 enzymes, particularly CYP2D6 and CYP3A4. Individuals with poor metabolizer status for CYP2D6 or low hepatic activity of CYP3A4 are at a higher risk of attaining toxic nortriptyline concentrations, even with standard dosing. This highlights the importance of genotyping and therapeutic drug monitoring to prevent accidental poisoning .
Conclusion
Nortriptyline interacts with several drugs through various mechanisms, primarily involving the cytochrome P450 enzyme system. These interactions can lead to significant changes in nortriptyline plasma concentrations, potentially resulting in enhanced therapeutic effects or increased toxicity. Clinicians should be aware of these interactions and consider appropriate monitoring and dosage adjustments to ensure patient safety.
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